title: Mutant Native Outer Membrane Vesicles Combined with a Serogroup A Polysaccharide Conjugate Vaccine for Prevention of Meningococcal Epidemics in Africa.
abstract: The meningococcal serogroup A (MenA) polysaccharide conjugate vaccine used in Sub-Saharan Africa does not prevent disease caused by MenW or MenX strains, which also cause epidemics in the region. We investigated the vaccine-potential of native outer membrane vesicles with over-expressed factor H-binding protein (NOMV-fHbp), which targeted antigens in African meningococcal strains, and was combined with a MenA polysaccharide conjugate vaccine.
  
  
  
  The NOMV-fHbp vaccine was prepared from a mutant African MenW strain with PorA P1.5,2, attenuated endotoxin (ΔLpxL1), deleted capsular genes, and over-expressed fHbp in variant group 1. The NOMV-fHbp was adsorbed with Al(OH)3 and used to reconstitute a lyophilized MenA conjugate vaccine, which normally is reconstituted with liquid MenC, Y and W conjugates in a meningococcal quadrivalent conjugate vaccine (MCV4-CRM, Novartis). Mice immunized with the NOMV-fHbp vaccine alone developed serum bactericidal (human complement) activity against 13 of 15 African MenA strains tested; 10 of 10 African MenX strains, 7 of 7 African MenW strains, and 6 of 6 genetically diverse MenB strains with fHbp variant group 1 (including 1 strain from The Gambia). The combination NOMV-fHbp/MenA conjugate vaccine elicited high serum bactericidal titers against the two MenA strains tested that were resistant to bactericidal antibodies elicited by the NOMV-fHbp alone; the combination elicited higher titers against the MenA and MenW strains than those elicited by a control MCV4-CRM vaccine (P<0.05); and high titers against MenX and MenB strains. For most strains, the titers elicited by a control NOMV-fHbp knock out vaccine were <1∶10 except when the strain PorA matched the vaccine (titers >1∶000).
  
  
  
  The NOMV-fHbp/MenA conjugate vaccine provided similar or higher coverage against MenA and MenW strains than a quadrivalent meningococcal conjugate vaccine, and extended protection against MenX strains responsible for epidemics in Africa, and MenB strains with fHbp in variant group 1.
authors.affiliation: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, United States of America.
authors.forename: Rolando
authors.initials: R
authors.lastname: Pajon
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fergus
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000818:Animals; D005260:Female; D006801:Humans; D008585:Meningitis, Meningococcal / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000235:genetics / Q000276:immunology; D051379:Mice; D038381:Neisseria meningitidis, Serogroup A / Q000235:genetics / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000276:immunology; D018074:Vaccines, Conjugate / Q000235:genetics / Q000276:immunology
chemical_list: D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; C043226:meningococcal group A polysaccharide